This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Epithelial-mesenchymal transition (EMT) occurs during normal embryonic development and epithelial tumor progression. Several factors associated with EMT contribute to motility, invasion, and angiogenesis, and may be important therapeutic targets for prostate cancer metastasis. Understanding the factors that contribute to EMT and prostate cancer metastasis is crucial for development of cancer therapies. For example, Snail transcription factor has been identified as an important factor that can induce EMT in breast and colon cancer. However, the role of EMT in prostate cancer is not well defined and good EMT models are lacking. Recently we have established an EMT model for prostate cancer progression using the ARCaP cell model overexpressing Snail. The goal of this proposal is to study the role of Snail transcription factor in prostate cancer progression and metastasis. We have found that Snail-induced EMT in prostate cancer cells involves reactive oxygen species (ROS) and receptor activator of NFkB (RANKL), two factors that are important in cancer disease progression and bone metastatic lesions, respectively. This proposal will elucidate the biological significance of Snail, with emphasis of its role in prostate cancer bone metastasis. In addition, we will characterize the signaling pathway of Snail-induced EMT, and finally examine the effect of antagonizing Snail expression on tumor aggressiveness in vitro and in vivo. We believe these studies will identify Snail as an attractive therapeutic target not only for EMT during primary tumor progression but also for bone metastatic lesions at the secondary site.